Abstract: FR-PO784
Parietal Epithelial Cell (PEC)-Specific Knockout of Integrin-αv Attenuates PEC Activation and Proliferation in Proliferative Glomerulopathy
Session Information
- Glomerular Diseases: Mechanisms and Podocyte Biology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Sathee, Deepa, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
- Krishnan, Anirudh, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
- Guo, Yiqing, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
- Bronstein, Robert, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
- Mallipattu, Sandeep K., Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
Background
Parietal epithelial cell (PEC) activation and proliferation contributes to crescent formation, leading to glomerulosclerosis and eventual loss of kidney function in proliferative glomerulopathies. Our previous single nucleus RNA-seq in mice with proliferative glomerulopathy demonstrated an enrichment in Integrin avb6 signaling in activated PECs. Here, we investigate the role of Itgav in PEC activation and proliferation in models of proliferative glomerulopathy.
Methods
Mouse PECs with Itgav knockdown (Itgav-/-) were generated by lentiviral method. RTPCR was employed for determining PEC activation markers. Scratch assay was performed to assess the migration pattern. PEC-specific inducible Itgav-/- mice were generated using the “tet-on” system. NTS (Nephrotoxic serum) was used as a model of proliferative glomerulopathy. Albuminuria, histopathological assessment for crescent formation, PEC markers and fibrotic markers were measured.
Results
Itgav-/- PECs showed a reduction in activated PEC markers (CD44, CD74, CCND1, DOCK10, FOSL2, CLDN1) as compared to control cells. In addition, Itgav-/- PECs exhibited changes in morphology, less proliferation (MTT, cell count) and migration as compared to control cells. PECs treated with monoclonal-ab against avb6 also attenuated PEC activation and proliferation. NTS-treated Itgav-/- mice showed a decrease in albuminuria at day 7 post-NTS as compared to NTS-treated WT mice, with a decrease in activated PECs (reduced CD44 expression) and fibrotic markers (α-SMA, picrosirius red).
Conclusion
These data suggest that loss of Itgav in PECs attenuates PEC activation, cell migration, crescent formation and eventual fibrosis in models of proliferative glomerulopathy.
Funding
- NIDDK Support